The scope of this project is to understand the molecular mode of action of vitamin A in controlling epithelial differentiation and growth. The following studies have been conducted in the past year. Phosphorylated derivatives of retinol and retinoic acid (retinoids) have been synthesized and studied for their ability to function as acceptors of D-mannose from guanosine diphosphate mannose in a reaction catalyzed by rat liver membranes. It was found that the phosphate esters of retinol and its derivatives were efficient acceptors of D-mannosyl residues. The mixed anhydrides of all-trans-beta-retinoic acid, 13-cis-retinoic acid and phosphoric acid did not function as mannosyl acceptors. Mannosyl retinyl phosphate was found to donate D-mannose to specific endogenous glycoproteins of the rat liver membranes. These glycoproteins were susceptible to pronase, yielding glycopetides. Another glycosyl derivative of the phosphorylated vitamin, galactosyl retinyl phosphate, was isolated from cultured epidermal cells. BIBLIOGRAPHIC REFERENCES: De Luca, L.M., Frot-Coutaz, J.P., Silverman-Jones, C.S., and Roller, P.R.: Chemical synthesis of phosphorylated retinoids: their mannosyl acceptors activity in rat liver membranes. J. Biol. Chem. 252: 2574-2579, 1977. Sundaresan, P.R. and De Luca, L.M.: Vitamin A contents of rat intestinal epithelium and jejunal mucinous adenocarcinoma. J. Natl. Cancer Inst. 1977, In press.